OSM-0205 is a patent-protected drug that modulates intracellular calcium via a novel mechanism. Chemotherapy treatment, which destroys cancer cells based on microtubule disruption, produces an intracellular calcium surge that damages neurons. OSM-0205, which is administered intravenously immediately prior to chemotherapy treatment, has the potential to protect neurons in patients by preventing this surge in intracellular calcium, thus improving patient quality-of-life as well optimizing chemotherapy.
Taxanes, such as paclitaxel, are often used in the treatment of breast cancer, prostate cancer, and other solid tumors. During treatment, taxanes bind to neuronal calcium sensor-1 (NCS1), resulting in a surge of calcium. This leads to calpain (a protease) activation, which degrades NCS1 and other proteins, resulting in neuronal atrophy.
Preclinical data shows that OSM-0205 blocks this calcium surge in mice and prevents calpain activation, thus maintaining NCS1 and other proteins and protecting neuronal integrity.
Proof of Concept in Preclinical Model—Behavior
Chronic taxane administration in mice leads to pathological and behavioral features similar to CIPN. A rotarod test (“log rolling”) was used to assess the ability of the mice to maintain balance, demonstrating their somatosensory neuronal function.
Pretreatment with parenteral OSM-0205 prevented taxane-induced rotarod deficits.1
Proof of Concept in Preclinical Model—Cognitive Impairment
Chemotherapy-induced cognitive impairment (CICI, also commonly known as chemo brain) frequently includes problems in attention, concentration, working memory, and executive function.2 The Morris water maze task (MWM) was used to assess the ability of mice to memorize its spatial relation to visual cues demonstrating spatial memory.3
Pretreatment with OSM-0205 in taxane-treated mice, prevented taxane-induced spatial memory deficits.4
Proof of Concept in Preclinical Model—Morphology
The neuronal fibers from mice treated with OSM-0205 (image on the left) show no damage whereas mice treated with paclitaxel (center image) have been damaged. Arrows indicate axons occupied by debris-filled phagocytes as a result of taxane treatment. Mice receiving OSM-0205 prior to paclitaxel treatment (image on the right) are protected from damage, appearing similar to healthy neuronal cells (image on the left).1